Trend and early clinical outcomes of off-pump coronary artery bypass grafting in the UK

Abstract OBJECTIVES The popularity of off-pump coronary artery bypass grafting (CABG) varies across the world, ranging from 20% in Europe and the USA to 56% in Asia. We present the trend and early clinical outcomes in off pump in the UK. METHODS All patients who underwent elective or urgent isolated CABG from 1996 to 2019 were extracted from the National Adult Cardiac Surgery Audit database. The trend in operating surgeons and units volume and training in off pump were analysed. Early clinical outcomes between off- and on-pump CABG were compared using propensity score matching. RESULTS A total of 351 422 patients were included. The overall off-pump rate during the study period was 15.17%, it peaked in 2008 (19.8%), followed by a steady decreased to 2018 (7.63%). Its adoption varied across centres and surgeons, ranging from <1% to 48.36% and <1% to 85.5%, respectively, of total cases performed. After propensity score matching for the period 1996–2019, off pump, when compared to on pump, was associated with a lower in-hospital/30-day mortality (1.2% vs 1.5%, P < 0.001), return to theatre (3.7% vs 4.5%, P < 0.001), cerebrovascular accident (transient ischaemic attack: 0.3% vs 0.6%, stroke: 0.3% vs 0.6%, P < 0.001) and deep sternal wound infection (0.8% vs 1.2%, P ≤ 0.001). In a sub-analysis from the introduction of EuroScore II (2012–2019), there were no differences in-hospital/30-day mortality (1.0% vs 1.0%, P = 0.71). However, on pump, had a higher return to theatre (4.2% vs 2.7%, P < 0.001), cerebrovascular accident (transient ischaemic attack: 0.4% vs 0.2%, stroke: 0.5% vs 0.3%, P = 0.003) and deep sternal wound infection (1.0% vs 0.6%, P = 0.004). CONCLUSIONS Our data show a decreasing trend in the use of off pump in the UK since 2008. This is likely to be multifactorial and raises the question of whether it should be a specialized revascularization technique.


INTRODUCTION
Coronary artery bypass grafting (CABG) is traditionally performed with cardiopulmonary bypass, allowing surgeons to operate on a bloodless field with an arrested heart.Off-pump coronary artery bypass (OPCAB) was first reported in the 1960s, with the operation performed on a beating heart [1].It has been suggested that by avoiding the inflammatory response from cardiopulmonary bypass, patients, particularly in certain high risks groups like octogenarians, those with pulmonary disease, poor left ventricular functions, high EuroScore II and porcelain aorta, could most benefit from OPCAB [2].
However, several randomized control trials (RCTs) and many retrospective cohort studies have not shown any conclusive major differences in short-and long-term mortality between the 2 revascularization techniques resulting in different popularity of OPCAB across the world, ranging from 20-25% in Europe and the USA to 50-70% in Asia [3,4].There are limited studies reporting the trend in OPCAB in recent years in the literature [5,6].We, therefore, aimed to present the trend and the early clinical outcomes in OPCAB in the UK over a 23-year period.Furthermore, using propensity score matching (PSM), we investigated differences in early clinical outcome between OPCAB and on-pump coronary artery bypass (ONCAB).

METHODS
All patients who underwent elective or urgent isolated CABG from April 1996 to April 2019 (in the UK data are collected according to the financial year April to April) were extracted from the National Adult Cardiac Surgery Audit (NACSA) database.The NACSA database prospectively collects data on all major heart operations carried out on National Health Service patients in the UK since April 1996.The definitions of database variables used, and a description of the database was previously described [7].Patients were divided into 2 groups: (i) ONCAB and (ii) OPCAB.Patients who underwent emergency or salvage CABG, non-isolated CABG and had previous cardiac surgery (re-do cases) were excluded from the study.Multiple arterial grafting was defined as > _2 arterial grafts used.Patients with missing data regarding the use of cardiopulmonary bypass (n = 9384, 2.69%) were also excluded from the analysis.The trend, early clinical outcomes, individual surgeon and unit volume and trainees' exposure to OPCAB technique were compared.The primary outcome was in-hospital/30-day mortality.Furthermore, using PSM, we compared the early clinical outcomes between the 2 revascularization techniques.Furthermore, we compared the short-term postoperative outcomes between the 2 revascularization techniques in certain high-risk groups-patients with preoperative pulmonary disease (chronic pulmonary disease requiring the use of long-term medication), poor left ventricular ejection fraction (<30%), extracardiac arteriopathy and EuroScore II> _4.Primary/ first operator should performed >= 50% of the total number of anastomosis.Trainee was defined as non-consultant surgeons, regardless of experience.
The observed mortality was compared against the expected mortality in all patients, and ONCAB and OPCAB groups.The observed mortality was defined as 30-day or in-hospital mortality after the index operation.The expected mortality was calculated using the EuroScore II.

Ethical statement
The study was part of a research project approved by the Health Research Authority and Health and Care Research Wales.As the study included retrospective interrogation of the NICOR database the need for individual patient consent was waived off (Health and Care Research Wales) (IRAS ID: 278171) in accordance with the research guidance.The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

Statistical analysis
Continuous variables are presented as mean [standard deviation (SD)] or median (interquartile range) and were compared using Student's t-test or Wilcoxon rank-sum test, as appropriate.Categorical variables are presented as numbers and frequencies and were compared using chi-squared exact test.Missing continuous variables data (body mass index, n = 23 527, left ventricular ejection fraction category, n = 6585) were imputed with the median value in the data after the application of exclusion criteria listed above, while categorical variable (gender n = 207) was imputed with the mode.
To account for potential imbalance in baseline risk, a propensity score was calculated for each patient based on a nonparsimonious logistic regression model.All variables included in the model are listed in Table 1.A 1:1 nearest-neighbour PSM without replacement and with a calliper width of 0.2 SDs of the logit of the propensity score was performed.After PSM, standardized mean difference was used to assess balance of the covariates between the ONCAB and OPCAB groups.A value higher than 0.10 was considered to indicate the presence of residual imbalance among variables.The covariate balance before and after as well as the effectiveness of the PSM was visualized (Supplementary Material, Figs S1 and S2).A generalized, linear model was used to evaluate the factors predicting the adoption of OPCAB.Results are demonstrated as odds ratio (OR) and 95% confidence interval (CI).In all the analyses, ONCAB was used as the reference group.R (Version 4.2.0) and R Studio (Version 1.4.1103,RStudio, PBC) were used to perform the statistical analysis.A P-value of <0.05 is deemed statistically significant.

RESULTS
A total of 351 422 patients were included in this study, of whom 53 301 (15.17%) underwent OPCAB.The number of OPCAB performed increased in the early 2000s.After it peaked in 2008, to 19.80%, the number gradually decreased afterwards to 7.63% in 2018 (Fig. 1).The mortality rate for all isolated CABG was 1.52% over the study period.The observed mortality rate was reduced from 2% in early 2000s to 1.12% in 2018 while the EuroScore II increased from 1.07% in 2000 to 1.82% in 2018.Figures 2 and 3 show, respectively, the observed and predicted mortality in all isolated CABG and separately for OPCAB from 2000 to 2018.
The mean cardiopulmonary bypass and aortic cross-clamp time in the ONCAB group was 83.81 (SD 33.70 min) and 48.80 (SD 21.76 min), respectively.The median and mean number of distal anastomosis performed in OPCAB and ONCAB were 3 and 2.51 and 3 and 3.01, respectively, P < 0.001.OPCAB was associated with a higher rate of multiple arterial grafting [34% vs 8.5%, P < 0.001].
In a subgroup analysis in patients with preoperative pulmonary disease, extracardiac arteriopathy and EuroScore II > _4, we found no differences in-hospital/30 day mortality or incidence of deep sternal wound infection between the 2 groups.However, a shortterm mortality benefit was shown in patients with poor left ventricular dysfunction (2.3% vs 3.0%, P = 0.001) undergoing OPCAB.The incidence of CVA in the OPCAB group was lower across all high-risk groups except for patients with EuroScore II > _4.Patients with poor LV and pulmonary disease who underwent OPCAB had a lower incidence of return to theatre [4.4% vs 5.8%, P < 0.001, and 4.6% vs 5.7%, P = 0.007, respectively].

Proportion of off-pump coronary artery bypass performed by trainees, individual hospital units and surgeons
Trainee exposure to OPCAB followed a similar pattern to the number of total OPCAB performed.The number of OPCAB performed by trainees peaked in 2009 with nearly 4% and then significantly reduced after 2013, with an average between 1.5% and 2% with trainees being the primary operator.Overall, 2.46% of OPCAB were performed by trainee compared with 26.2% of ONCAB.
The proportion of OPCAB performed varied significantly between centres, ranging from 0.52% to 48.36% of total cases.The 2 highest volume centres performed >40% of their cases off pump, while the 3rd and 4th highest performed <10% of cases (Fig. 4).Similarly, the top 2 surgeons, who recorded >2400 cases each, performed 80% and 65% of their cases off pump.Of the 82 surgeons who recorded >1000 isolated CABG, 15 (18%) performed more than half of their overall cases using off-pump technique (Table 4).More than half surgeons (n = 45) performed >95% of their cases with cardiopulmonary bypass.Table 5 shows the number of OPCAB performed in centres which logged >10000 cases.

DISCUSSION
Our study demonstrated a reduction in popularity in OPCAB across the study period in the UK.Several reasons could explain our findings: First, OPCAB has failed to demonstrate short and long-term survival benefits compared with ONCAB in RCTs.No differences were shown in terms of symptoms, generic and disease-specific quality of life between OPCAB and ONCAB in the midterm follow-up in the BHACAS (Beating heart against cardioplegic arrest studies) 1 and 2 trials [8].The long-term follow-up in ROBBY and CORONARY trial showed no advantages in terms of survival and repeat revascularization between the 2 techniques [9,10].Similar results were reported in the subgroup analysis from the ART trial [11].Raja et al. in a single-centre study reported their 20-year follow-up comparing OPCAB and ONCAB which, again, showed no differences between the 2 techniques [12].In fact, OPCAB was often associated with a lower number of graft and increased risk of incomplete revascularization.Incomplete revascularization is known to be independently associated with a poorer long-term survival and increased the need for repeat revascularization [13][14][15].The analysis for the time period 1996-2019 showed that OPCAB, when compared to ONCAB, was associated with a significantly lower in-hospital/30-day mortality.However, similar to most retrospective studies, and RCTs no differences between ONCAB and OPCAB were identified in early  mortality when a sub-analysis was conducted after the introduction of EuroScore II (2012-2019).
Although most studies rightly focuses on mortality, incidence of repeat revascularization and major adverse cardiovascular events (MACEs), there seems to be general agreement that OPCAB reduces the incidence of early clinical outcomes like low cardiac output, postoperative renal dysfunction, need for red cell transfusion and length of intensive care unit and hospital stay [16].We found that patients undergoing OPCAB had a reduced incidence of return to theatre, deep sternal wound infection and postoperative cerebral vascular accident (CVA).OPCAB also seems to be of benefit in several high-risk groups.Naito et al. showed that, in experience OPCAB centres, there was a lower post-procedural acute kidney injury, shorter duration of intensive care unit stay and lower 30-day mortality [17].In patients with high surgical risk, meta-analyses have observed reduced perioperative morbidity and mortality [18], especially for those in the highest-risk quartiles [19].Similarly, in large retrospective studies, patients with impaired ventricular function undergoing OPCAB have shown a reduced risk in mortality, CVA and MACEs [20,21].As a result, the 2018 ESC/EACTS Guidelines on myocardial revascularization recommended OPCAB for subgroups of high-risk patients to be performed by experienced off-pump teams (class IIa, level B) [22].
The trend in OPCAB varies worldwide.In the USA, OPCAB use has reduced to almost half of the initial rate over a 15-year period in Veterans Affairs medical centres [5].Only 8/43 (18%) centres used OPCAB for >30% of the total cases and 3/25 (12%) did not perform OPCAB at all.A similar trend was reported by the STS (Society of Thoracic Surgeons) database.Only   increased from 13.1% in 2009 to 23.85% in 2021 [23].The OPCAB reported rate was 53-61.0% in Korea [24,25] and 55.0% in Japan [26].
The trend in the UK indicates that OPCAB is performed routinely by a small group of surgeons.Only 18% of surgeons, who logged >1000 procedures, performed >50% of their cases without the use of cardiopulmonary bypass.Similarly, only 2 units performed >40% of the total cases using off-pump technique.Multiple studies have reported that the volume of OPCAB plays an important role in clinical outcomes.Benedetto et al. [27] suggested that clinical outcomes of OPCAB are highly dependent on the volume of OPCAB performed at both the institution and the individual surgeon levels.A sub-analysis in the ART trials also suggested a similar 10-year outcome between the 2 revascularization technique when performed by experienced surgeons [11].
OPCAB is not an easy surgery, and it is acknowledged that it involves a great deal of surgical dexterity and skill [28].Similar to multiple arterial revascularization, OPCAB requires dedication, infrastructure, and expertise to achieve proficiency and good results.This in turn raises the question: can OPCAB simply be introduced into routine clinical practice, or should it be a specialized technique?This, again, raises the question on the need for coronary specialists in each individual centre [4].
Percutaneous coronary interventions are now being routinely offered to patients with multivessel and/or left main coronary artery disease.Therefore, future patients requiring CABG will more likely have complex coronary artery disease [17,22].Furthermore, it is expected that the incidence of high-risk profile patients with atherosclerotic aorta, reduced left ventricular ejection fraction, stroke and/ or renal failure will continue to rise.Having a unit experienced OPCAB team that performs OPCAB routinely would benefit this cohort of patients.
A lack of exposure to OPCAB in the training program is likely to be another reason to explain the observed trend.Previous studies showed that OPCAB can be safely performed by trainee under supervision by senior surgeons within a dedicated training program [29,30].However, except for a few dedicated units that offer fellowship training, to the best of our knowledge, there are no national societies that have included OPCAB in the training curriculum [3,4].An unpublished trainee survey in the UK (75% response rate, n = 105) showed that training in OPCAB is variable across training programs with only 23.1% of respondents receiving formal training.This correlates with our finding of <2% of OPCAB performed by trainees in the past few years.Without a dedicated OPCAB training fellowship by coronary specialists, this decreasing trend is likely to continue.

Limitations
There are several limitations to our study.This study is subject to all the limitations associated with observation medical study with operations extending over 23 years.During this time, the perioperative management and surgical techniques for both OPCAB and ONCAB have evolved significantly.The anatomy of the coronaries was not recorded on the database and this could have influenced the decision to perform the operation with/without the use of cardiopulmonary bypass.Another major limitation is the conversion from off pump to on pump which is known to  increase the risk of death and serious complications.However, from our experience, the conversion is around <1%, and given the large number of patients included in the analysis, the effect should also be minimal [31].
The NACSA database heavily relies on healthcare professionals' input and some data were missing in some parts of the analysis.This is particularly apparent in the postoperative outcome and some of the non-mandatory options in the database.A small amount (<5%) of data on cardiopulmonary bypass use was missing and required to be excluded from the analysis.Despite the application of PSM, residual bias may be present in the analysis since the propensity-matched model can account only for measured confounders and not for the unmeasured confounders (e.g.frailty).The absence of conversion from off pump to on pump, long-term follow-up data showing survival rate, the need for revascularization and major adverse cardiac events rate are another limitation.Nevertheless, we believe that our study is an important topic in surgical practice worldwide.

CONCLUSION
Our data show a decreasing trend in the use of OPCAB in the UK since 2008.This reduction is likely to be multifactorial and raises the question of whether OPCAB should be a specialized revascularization technique.OPCAB remains a good complementary coronary revascularization technique with low mortality and early clinical complications.

Figure 1 :
Figure 1: The proportion of off-pump coronary artery bypass graft (blue) and on-pump coronary artery bypass (orange) and total number of isolated coronary artery bypass graft (grey) performed in the UK from 2000 to 2018.

Figure 3 :
Figure 3: The predicted mortality rate (Series 2) and the observed mortality rate (Series 1) for off-pump coronary artery bypass graft from 2000 to 2018.

Figure 4 :
Figure 4:The number of total isolated coronary artery bypass graft recorded (x-axis) and the proportion of cases performed using off-pump coronary artery bypass graft (y-axis) in each individual centre in the UK.

Table 1 :
The preoperative characteristics between off-pump coronary artery bypass graft and on-pump coronary artery bypass before and after propensity score matching
17 867 (11.66%) of CABG was performed off pump in 2022, a reduction from 30 730 (19.11%) in 2010.Following a different trend, the use of OPCAB in Germany has The predicted mortality rate (Series 2) and the observed mortality rate (Series 1) for all isolated coronary artery bypass graft from 2000 to 2018.

Table 2 :
The intra-and postoperative outcome between off-pump coronary artery bypass graft and on-pump coronary artery bypass after propensity score matching

Table 3 :
The intra-and postoperative outcome between off-pump coronary artery bypass graft and on-pump coronary artery bypass in cases performed between 2012 and 2019 after propensity score matching CPB: cardiopulmonary bypass; CVA: cerebrovascular accident; DSWI: deep sternal wound infection; N/A: not applicable; OPCAB: off-pump coronary artery bypass grafting; ONCAB: on-pump coronary artery bypass grafting; PSM: propensity score matching; RTT: return to theatre; SD: standard deviation; XClamp: cross-clamp.

Table 4 :
The 15 surgeons with the highest number of isolated coronary artery bypass graft logged and the proportion of cases performed using off-pump coronary artery bypass graft CABG: coronary artery bypass graft; OPCAB: off-pump coronary artery bypass graft.